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Investigating how mechanical connectivity yields developmental robustness

Award Number: R00GM136915
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Investigating how mechanical connectivity yields developmental robustness - ABSTRACT It is essential for the fate of an organism that key morphogenetic processes occur reproducibly even under tissue damage or environmental perturbations. While much is known about how genetic redundancy and regulation achieves robust development, less is understood about how a tissue mechanically ensures reproducible shape change when perturbed. This project uncovers how populations of physically interacting cells mechanically respond to challenging conditions and modify their collective behavior to still sculpt the correct final shape. One way for cells to coordinate tissue-scale forces and movements is through direct mechanical connections. In fact, many developing tissues exhibit supracellular networks of actomyosin connections that link hundreds of cells. A large roadblock has been with the challenges of imaging and quantifying subcellular protein at the tissue scale. I adapted a topological smoothing algorithm originally used to trace high-noise filamentous structure of galaxies in the Universe to data to trace high-noise filamentous myosin structure in confocal images. This allowed for the first quantification of a supracellular myosin network across an entire tissue over developmental time. Subsequent analysis adopting techniques from network theory allowed me to identify that the robust folding of the Drosophila fruit fly embryo during ventral furrow formation is mechanically ensured by patterns in the supracellular network spanning its ventral cells. This newly discovered importance of supracellular networks in coordinating robust shape change highlights the need for a comprehensive understanding of how supracellular networks form, and how their patterns impact the function and robustness of a population of cells. Deciphering robustness at the tissue-level, where the displacement and fate of hundreds of cells must be considered, requires techniques at the interface of cell and developmental biology, biophysics and computer science. The proposed project will take a highly interdisciplinary approach to identify how supracellular network patterns are controlled molecularly, at the cell level, and via tissue constraints. As well, how heterogeneity in tissue-level patterns impacts morphogenetic robustness will be addressed. Together this comprehensive study of the structure and function of supracellular networks will represent a new way to interpret mechanical robustness across diverse developing tissues. As well, a generalized description of mechanical robustness has the potential to uncover new paths to predict and control tissue malformation, which would represent a significant advance for both developmental biology and fetal medicine.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $224,101 )
2025	2025	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Biomedical Research and Research Training	000	5	12/18/2024	NON-COMPETING CONTINUATION	$224,101
														Subtotal = $224,101

Issue Date FY: 2024 ( Subtotal = $249,000 )
2024	2024	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Biomedical Research and Research Training	000	4	1/5/2024	NON-COMPETING CONTINUATION	$224,101
2024	2024	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Biomedical Research and Research Training	001	4	6/17/2024	NON-COMPETING CONTINUATION	$24,899
														Subtotal = $249,000

Issue Date FY: 2023 ( Subtotal = $287,662 )
2023	2023	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Biomedical Research and Research Training	001	3	7/24/2023	EXTENSION WITH OR WITHOUT FUNDS	$38,663
2023	2023	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Biomedical Research and Research Training	000	3	1/9/2023	EXTENSION WITH OR WITHOUT FUNDS	$248,999
														Subtotal = $287,662

Grand Total All Awards = $760,763

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Investigating how mechanical connectivity yields developmental robustness

Award Number: R00GM136915

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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